Genetic Variant ELAVL1:p.Arg131Gln (chr19-7973763-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001419.3(ELAVL1):c.392G>A(p.Arg131Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

ELAVL1
NM_001419.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

Variant links:

Genes affected

ELAVL1 (HGNC:3312): (ELAV like RNA binding protein 1) The protein encoded by this gene is a member of the ELAVL family of RNA-binding proteins that contain several RNA recognition motifs, and selectively bind AU-rich elements (AREs) found in the 3' untranslated regions of mRNAs. AREs signal degradation of mRNAs as a means to regulate gene expression, thus by binding AREs, the ELAVL family of proteins play a role in stabilizing ARE-containing mRNAs. This gene has been implicated in a variety of biological processes and has been linked to a number of diseases, including cancer. It is highly expressed in many cancers, and could be potentially useful in cancer diagnosis, prognosis, and therapy. [provided by RefSeq, Sep 2012]

ELAVL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34906626).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAVL1	NM_001419.3 link	c.392G>A	p.Arg131Gln	missense_variant	Exon 4 of 6	ENST00000407627.7	NP_001410.2	Q15717-1
ELAVL1	XM_047438383.1 link	c.473G>A	p.Arg158Gln	missense_variant	Exon 4 of 6		XP_047294339.1
ELAVL1	XM_047438384.1 link	c.473G>A	p.Arg158Gln	missense_variant	Exon 4 of 5		XP_047294340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAVL1	ENST00000407627.7 link	c.392G>A	p.Arg131Gln	missense_variant	Exon 4 of 6	1	NM_001419.3	ENSP00000385269.1		Q15717-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251326

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000773

AC:

113

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.392G>A (p.R131Q) alteration is located in exon 4 (coding exon 3) of the ELAVL1 gene. This alteration results from a G to A substitution at nucleotide position 392, causing the arginine (R) at amino acid position 131 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.;L;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

D;.;.;.

REVEL

Benign

0.14

Sift

Benign

0.12

T;.;.;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.19

B;.;B;.

Vest4

0.47

MutPred

0.39

Gain of sheet (P = 0.0149);.;Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.72

MPC

1.6

ClinPred

0.74

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.32

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over